Tos4 mediates gene expression homeostasis through interaction with HDAC complexes independently of H3K56 acetylation

Saccharomyces cerevisiae exhibits gene expression homeostasis, which is defined as the buffering of transcription levels against changes in DNA copy number during the S phase of the cell cycle. It has been suggested that S. cerevisiae employs an active mechanism to maintain gene expression homeostasis through Rtt109-Asf1-dependent acetylation of histone H3 on lysine 56 (H3K56). Here, we show that gene expression homeostasis can be achieved independently of H3K56 acetylation by Tos4 (Target of Swi6-4). Using Nanostring technology, we establish that Tos4-dependent gene expression homeostasis depends on its forkhead-associated (FHA) domain, which is a phosphopeptide recognition domain required to bind histone deacetylases (HDACs). We demonstrate that the mechanism of Tos4-dependent gene expression homeostasis requires its interaction with the Rpd3L HDAC complex. However, this is independent of Rpd3’s well-established roles in both histone deacetylation and controlling the DNA replication timing program, as established by deep sequencing of Fluorescence-Activated Cell Sorted (FACS) S and G2 phase populations. Overall, our data reveals that Tos4 mediates gene expression homeostasis through its FHA domain-dependent interaction with the Rpd3L complex, which is independent of H3K56ac

Effects of crossed electric and magnetic fields on the electronic and excitonic states in bulk GaAs and GaAs/Ga1-xAlxAs quantum wells

The variational procedure in the effective-mass and parabolic-band approximations is used in order to investigate the effects of crossed electric and in-plane magnetic fields on the electronic and exciton properties in semiconductor heterostructures. Calculations are performed for bulk GaAs and GaAs/Ga1-xAlxAs quantum wells, for applied magnetic fields parallel to the layers and electric fields in the growth direction, and it is shown that the combined effects on the heterostructure properties of the applied crossed electric and magnetic fields and the direct coupling between the center-of-mass and internal exciton motions may be dealt with via a simple parameter representing the spatial distance between the centers of the electron and hole magnetic parabolas. Exciton properties are analyzed by using a simple hydrogenlike envelope excitonic wave function and present theoretical results are found in fair agreement with available experimental measurements on the diamagnetic shift of the photoluminescence peak position of GaAs/Ga1-xAlxAs quantum wells under in-plane magnetic fields.75

Socioeconomic status and the incidence of non-central nervous system childhood embryonic tumours in Brazil

<p>Abstract</p> <p>Background</p> <p>Childhood cancer differs from most common adult cancers, suggesting a distinct aetiology for some types of childhood cancer. Our objective in this study was to test the difference in incidence rates of 4 non-CNS embryonic tumours and their correlation with socioeconomic status (SES) in Brazil.</p> <p>Methods</p> <p>Data was obtained from 13 Brazilian population-based cancer registries (PBCRs) of neuroblastoma (NB), Wilms'tumour (WT), retinoblastoma (RB), and hepatoblastoma (HB). Incidence rates by tumour type, age, and gender were calculated per one million children. Correlations between social exclusion index (SEI) as an indicator of socioeconomic status (SES) and incidence rates was investigated using the Spearman's test.</p> <p>Results</p> <p>WT, RB, and HB presented with the highest age-adjusted incidence rates (AAIRs) in 1 to 4 year old of both genders, whereas NB presented the highest AAIR in ≤11 month-olds. However, differences in the incidence rates among PBCRs were observed. Higher incidence rates were found for WT and RB, whereas lower incidence rates were observed for NB. Higher SEI was correlated with higher incidences of NB (0.731; p = 0.0117), whereas no SEI correlation was observed between incidence rates for WT, RB, and HB. In two Brazilian cities, the incidence rates of NB and RB were directly correlated with SEI; NB had the highest incidence rates (14.2, 95% CI, 8.6-19.7), and RB the lowest (3.5, 95% CI, 0.7-6.3) in Curitiba (SEI, 0.730). In Natal (SEI, 0.595), we observed just the opposite; the highest incidence rate was for RB and the lowest was for NB (4.6, 95% CI, 0.1-9.1).</p> <p>Conclusion</p> <p>Regional variations of SES and the incidence of embryonal tumours were observed, particularly incidence rates for NB and RB. Further studies are necessary to investigate risk factors for embryonic tumours in Brazil.</p

Radiating Shear-Free Gravitational Collapse with Charge

We present a new shear free model for the gravitational collapse of a spherically symmetric charged body. We propose a dissipative contraction with radiation emitted outwards. The Einstein field equations, using the junction conditions and an ansatz, are integrated numerically. A check of the energy conditions is also performed. We obtain that the charge delays the black hole formation and it can even halt the collapse.Comment: 22 pages, 9 figures. It has been corrected several typos and included several references. Accepted for publication in GR

Excitons and shallow impurities in GaAs-Ga1-xAlxAs semiconductor heterostructures within a fractional-dimensional space approach: Magnetic-field effects

The fractional-dimensional space approach is extended to study exciton and shallow-donor states in symmetric-coupled GaAs-Ga1-xAlxAs multiple quantum wells. In this scheme, the real anisotropic 'exciton (or shallow donor) plus multiple quantum well' semiconductor system is mapped, for each exciton (or donor) state, into an effective fractional-dimensional isotropic environment, and the fractional dimension is essentially related to the anisotropy of the actual semiconductor system. Moreover, the fractional-dimensional space approach was extended to include magnetic-field effects in the study of shallow-impurity states in GaAs-Ga1-xAlxAs quantum wells and superlattices. In our study, the magnetic field was applied along the growth direction of the semiconductor heterostructure, and introduces an additional degree of confinement and anisotropy besides the one imposed by the heterostructure barrier potential. The fractional dimension is then related to the anisotropy introduced both by the heterostructure barrier potential and magnetic field. Calculations within the fractional-dimensional space scheme were performed for the binding energies of 1s-like heavy-hole direct exciton and shallow-donor states in symmetric-coupled semiconductor quantum wells, and for shallow-impurity states in semiconductor quantum wells and superlattices under growth-direction applied magnetic fields. Fractional-dimensional theoretical results are shown to be in good agreement with previous variational theoretical calculations and available experimental measurements.6119131041311

Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Free Rhodium (II) citrate and rhodium (II) citrate magnetic carriers as potential strategies for breast cancer therapy

<p>Abstract</p> <p>Background</p> <p>Rhodium (II) citrate (Rh₂(H₂cit)₄) has significant antitumor, cytotoxic, and cytostatic activity on Ehrlich ascite tumor. Although toxic to normal cells, its lower toxicity when compared to carboxylate analogues of rhodium (II) indicates Rh₂(H₂cit)₄as a promising agent for chemotherapy. Nevertheless, few studies have been performed to explore this potential. Superparamagnetic particles of iron oxide (SPIOs) represent an attractive platform as carriers in drug delivery systems (DDS) because they can present greater specificity to tumor cells than normal cells. Thus, the association between Rh₂(H₂cit)₄and SPIOs can represent a strategy to enhance the former's therapeutic action. In this work, we report the cytotoxicity of free rhodium (II) citrate (Rh₂(H₂cit)₄) and rhodium (II) citrate-loaded maghemite nanoparticles or magnetoliposomes, used as drug delivery systems, on both normal and carcinoma breast cell cultures.</p> <p>Results</p> <p>Treatment with free Rh₂(H₂cit)₄induced cytotoxicity that was dependent on dose, time, and cell line. The IC₅₀values showed that this effect was more intense on breast normal cells (MCF-10A) than on breast carcinoma cells (MCF-7 and 4T1). However, the treatment with 50 μM Rh₂(H₂cit)₄-loaded maghemite nanoparticles (Magh-Rh₂(H₂cit)₄) and Rh₂(H₂cit)₄-loaded magnetoliposomes (Lip-Magh-Rh₂(H₂cit)₄) induced a higher cytotoxicity on MCF-7 and 4T1 than on MCF-10A (p < 0.05). These treatments enhanced cytotoxicity up to 4.6 times. These cytotoxic effects, induced by free Rh₂(H₂cit)₄, were evidenced by morphological alterations such as nuclear fragmentation, membrane blebbing and phosphatidylserine exposure, reduction of actin filaments, mitochondrial condensation and an increase in number of vacuoles, suggesting that Rh₂(H₂cit)₄induces cell death by apoptosis.</p> <p>Conclusions</p> <p>The treatment with rhodium (II) citrate-loaded maghemite nanoparticles and magnetoliposomes induced more specific cytotoxicity on breast carcinoma cells than on breast normal cells, which is the opposite of the results observed with free Rh₂(H₂cit)₄treatment. Thus, magnetic nanoparticles represent an attractive platform as carriers in Rh₂(H₂cit)₄delivery systems, since they can act preferentially in tumor cells. Therefore, these nanopaticulate systems may be explored as a potential tool for chemotherapy drug development.</p

Salivary characteristics may be associated with burning mouth syndrome?

Burning mouth syndrome (BMS) it is characterized by burning and uncomfortable sensations with no clinical alterations or laboratory findings. The evaluation of the salivary characteristics of people with BMS can help the understanding of the pathogenesi

Sustainable multifunctional phenolic lipids as potential therapeutics in Dentistry

Phenolic lipids components of the cashew nutshell liquid (CNSL) have molecular structures capable of chemical signalling that regulate gene expression, metabolism and inflammation. This study sets out to assess how CNSL derivatives impact oral bacteria, from an antibacterial and anti-collagenolytic perspective, as well as its biocompatibility with dental pulp stem cells. Two hemi-synthetic saturated CNSL derivative compounds were selected (LDT11-Anacardic Acids-derivative and LDT409-cardanol-derivative). Bacteriostatic activity was tested against Streptococcus mutans and Veillonella parvula. Antimicrobial capacity against preformed S. mutans biofilms was investigated using a collagen-coated Calgary Biofilm Device and confocal microscopy. Clostridium histolyticum, P. gingivalis and S. mutans biofilms were used to assess anti-collagenolytic activity. Biocompatibility with human dental pulp stromal cells (HDPSCs) was investigated (MTT for viability proportion, LDH assays for cell death rate). LDTs inhibited the bacterial growth, as well as partially inhibited bacterial collagenases in concentrations higher than 5 μg/mL. Dose–response rates of biofilm cell death was observed (LDT11 at 20, 50, 100 μg/mL = 1.0 ± 0.4, 0.7 ± 0.3, 0.6 ± 0.03, respectively). Maximum cytotoxicity was 30%. After 1 week, LDT409 had no HDPSCs death. HDPSCs viability was decreased after 24 h of treatment with LDT11 and LDT409, but recovered at 72 h and showed a massive increase in viability and proliferation after 1 week. LDTs treatment was associated with odontoblast-like morphology. In conclusion, LDT11 multifunctionality and biocompatibility, stimulating dental pulp stem cells proliferation and differentiation, indicates a potential as a bio-based dental material for regenerative Dentistry. Its potential as a bacterial collagenases inhibitor to reduce collagen degradation in root/dentinal caries can be further explored